I. What every physician needs to know.

Necrotizing cellulitis, myositis, and necrotizing fasciitis are types of necrotizing soft-tissue infections (NSTIs). NSTIs typically arise in fascia or muscle, rather than in the more superficial dermis or epidermis. The source of these infections is usually skin trauma or an existing lesion (such as an ulcer). These infections most often develop in the perineum, extremities, and genitalia, but they can occur anywhere in the body.

Several names have been used for NSTIs (including suppurative fasciitis, Fournier’s gangrene, clostridial infection, and streptococcal infection), depending on the affected body part, the causative pathogen, and the level at which the infection occurs (for example, cellulitis versus myositis). This has led to some confusion, since NSTIs have a similar pathologic basis underlying their development, and require similar treatment modalities irrespective of the body part on which they are located.

An important characteristic of NSTIs is the rapidly progressive and widespread destruction of the subcutaneous tissue and fascia that occurs. The severity of systemic symptoms that develop with a NSTI depends on the toxins generated by the infecting bacteria. When a NSTI is suspected, then prompt surgical exploration with aggressive debridement is essential. Also, required for the proper management of NSTIs are the immediate initiation of intravenous antibiotic therapy, and the provision of adequate hemodynamic support.

Unfortunately, despite the provision of optimal therapy, NSTIs are associated with mortality rates that are between 16% and 35%. Furthermore, if surgical debridement is not performed, then the mortality rate will be close to 100%.

Type I NSTI is a polymicrobial infection, which includes at least one anaerobic pathogen (such as Clostridium or Bacteroides), one or more types of Enterobacteriaceae (such as Klebsiella and Escherichia coli), and Streptococcus (not group A). It is most commonly seen in post-surgical patients, as well as those who have peripheral vascular disease or diabetes mellitus. Fournier’s gangrene (which develops in the perineal area) is an example of type I NSTI. Another example of type I NSTI is cervical necrotizing fasciitis, which often develops following oral surgery, or as a result of an odontogenic infection.

Type II NSTI occurs less frequently than type I NSTI, and is most commonly due to group A β-hemolytic Streptococcus species. Staphylococcus aureus also has been identified as a cause of type II NSTI, either by itself, or in combination with group A β-hemolytic streptococcal species. Unlike type I necrotizing fasciitis, which has a propensity to occur in patients with chronic illnesses, or who are otherwise immunocompromised, type II NSTI tends to develop in healthier and younger patients. These patients are more likely to have a history of intravenous (IV) drug use, trauma, and surgery than are those who develop type I NSTI. Streptococcal toxic shock syndrome may develop in these patients, and this may necessitate very aggressive hemodynamic support.

Type III NSTI is most commonly due to Vibrio vulnificus, a gram-negative marine organism. This class of NSTI is not as widely accepted as types I and II. Similar to patients with type II NSTIs, those with type III NSTIs may develop severe systemic complications, including multisystem organ failure, very early during their illness.

A substantial number (that is, greater than 20 percent) of patients with NSTI have “idiopathic” NSTI, since no causative pathogen can be identified.

Clostridial myonecrosis or "gas gangrene" is a life-threatening infection which affects the skeletal muscle and is most commonly caused by Clostridium species. It typically develops adjacent to a site of trauma, or as result of the hematogenous spread of bacteria from the gastrointestinal tract into the muscle. The two most common presentations of clostridial gas gangrene are spontaneous and traumatic.

70% of cases of traumatic gas gangrene develop following a traumatic injury (such as a gunshot or knife wound, or a crush injury) that deeply penetrates the body and leads to a decrease in the vascular supply to the affected area. Clostridium perfringens, which is responsible for 80% of the cases of traumatic gas gangrene, grows well in this anaerobic milieu. As is true for a NSTI, appropriate management of traumatic gas gangrene includes prompt surgical exploration and debridement, antibiotics and supportive care. Mortality is higher if the traumatic gas gangrene affects the trunk or viscera, rather than an extremity, since the latter is more readily debrided.

Spontaneous gas gangrene develops in the absence of a traumatic injury. It is usually caused by Clostridium septicum, and typically develops in a patient who has a colon malignancy. Spontaneous gas gangrene occurs when a lesion in the gastrointestinal tract facilitates the hematogenous spread of the bacteria from this damaged site to the muscle. Clostridium septicum does not require an anaerobic environment for growth. Prompt surgical debridement and antibiotic therapy are essential for proper management. The mortality rate associated with spontaneous gas gangrene is between 67-100%.

Intense pain and tenderness over involved skin and underlying muscle (which is out of proportion to the appearance of the skin).

Blisters/bullae.

Crepitus.

Subcutaneous gas.

Tense edema (over the affected area of skin).

Although the above findings have fair specificity, their sensitivity is only 10 to 40%.

Gas gangrene findings

For traumatic gas gangrene:

Crepitus (most sensitive and specific clinical examination finding).

Acute onset of pain in area affected by trauma.

Skin discoloration (initially pale, then bronze, then purple or red).

Tense skin.

Bullae.

Evidence of systemic toxicity.

For spontaneous gas gangrene:

Acute development of intense muscle pain (without any preceding trauma).

Fever.

A. History Part I: Pattern Recognition:

NSTI pattern recognition

For NSTI:

Pain (often out of proportion to skin findings).

Swelling.

Fever.

Erythema.

Induration.

Crepitus.

Purulent discharge.

Skin sloughing.

Blistering necrosis.

Cyanosis.

Poor response to therapy.

Tachycardia (in later stages).

Mental status changes (in later stages).

Hypotension (may be present either initially, or in later stages).

Weakness (in later stages).

Diarrhea.

Malaise.

Myalgias.

Anorexia.

Gas gangrene pattern recognition

For traumatic gas gangrene:

Pain (often out of proportion to skin findings).

Skin discoloration (initially pale, then bronze, then purple or red).

Tense skin.

Bullae (can be purple, blue, red or clear).

Tachycardia (can be seen on presentation).

Fever (can be seen on presentation).

Shock (can be seen on presentation).

Multisystem organ failure (can be seen at presentation).

For spontaneous gas gangrene:

Sudden onset of intense muscle pain.

Confusion.

Malaise.

Edema.

Bullae (the skin around these has a purplish discoloration).

Crepitus.

Fever.

B. History Part 2: Prevalence:

NSTI prevalence

An estimated 500 to 1500 cases of NSTIs occur in the United States each year. The incidence rate of necrotizing invasive group A Streptococcus infections is 3.5 cases per 100,000 people. No definite risk factors have been confirmed for the development of NSTIs, but they have been associated with several conditions:

Diabetes.

Major trauma.

Peripheral vascular disease.

Intravenous drug abuse.

Recent surgery.

Chronic alcohol abuse.

Immunosuppression (including corticosteroid use).

Liver cirrhosis.

Malnutrition.

Obesity.

Malignancy.

Perforated viscus.

NSTI is more likely to develop following:

Skin laceration.

Childbirth.

Spider bite.

Surgery.

Burn injury.

Liposuction.

Varicella virus infection, which is associated with bacterial superinfection.

Exposure to seawater, or consumption of seafood that is contaminated by Vibrio vulnificus.

Skin laceration.

Gas Gangrene prevalence

Traumatic gas gangrene is associated with:

Traumatic injury (most cases).

Intrauterine fetal demise.

Retained placenta.

Intramuscular injection.

Abortion.

Bowel and biliary tract surgery.

Black tar heroin injection ("skin popping").

Spontaneous gas gangrene is associated with:

Diverticulitis.

Necrotizing enterocolitis, cecitis, distal ileitis.

Leukemia.

Colonic malignancy.

Inflammatory bowel disease.

Lymphoproliferative disorders.

Chemotherapy.

Gastrointestinal surgery.

Neutropenia.

Radiation therapy.

Acquired immunodeficiency syndrome (AIDS).

C. History Part 3: Competing diagnoses that can mimic Necrotizing Soft-Tissue Infections and Gas Gangrene.

NSTI differential diagnosis

For NSTI, the differential diagnosis includes:

Clostridial myonecrosis.

For clostridial myonecrosis, the differential diagnosis includes:

Necrotizing fasciitis.

Pyomoyositis.

Rhabdomyolysis.

Anaerobic cellulitis.

D. Physical Examination Findings.

For necrotizing fasciitis:

Intense pain and tenderness over the involved skin and underlying muscle (out of proportion to the appearance of the skin).

Edema extending beyond the area of erythema.

Blisters/bullae.

Crepitus.

Subcutaneous tissue has a wooden, hardened texture (so that is not possible to detect fascial planes and muscle groups by palpation).

Fever and systemic toxicity.

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Complete blood count (CBC).

Basic metabolic panel (BMP).

Arterial blood gas (ABG).

For patients with a NSTI, percutaneous needle aspiration (taken from the leading edge of the infection), followed by immediate performance of Gram’s staining and culture.

The results of this test are not as reliable as those obtained from tissue that is collected during surgery.

Blood cultures (are positive in 20% of patients with type I NSTI, and in about 60% of patients with type II NSTI).

Even when positive blood culture results are obtained, they cannot be used to definitively guide the selection of antibiotics. For patients with traumatic gas gangrene, bacteremia occurs 15% of the time.

Tissue cultures are to be obtained during surgical debridement procedures for NSTI and traumatic gas gangrene.

To confirm the diagnosis of both traumatic and spontaneous gas gangrene, gram-variable rods must be detected at the affected site.

C-reactive protein (CRP).

Creatinine phosphokinase (CPK).

Microscopic examination of the biopsy specimens obtained during surgical debridement may be performed to help confirm the diagnosis.

The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) model utilizes the white blood cell count, hemoglobin, creatinine, sodium, CRP and glucose to predict the likelihood that a patient has a NSTI. A patient with an LRINEC score of 6 or 7 is at intermediate risk for having a NSTI, while a score ≥ 8 is highly predictive of this diagnosis. It is important to recognize that use of the LRINEC score is limited if the patient has a co-existing illness that produces inflammation. The LRINEC score should not be used alone as a basis for management decisions.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

It is important that surgical exploration should not be delayed to obtain imaging studies.

The presence of gas in the tissue is most commonly noted with Clostridial myonecrosis (gas gangrene), and to a lesser degree with type I NSTI, and this finding can help to confirm the suspected diagnosis. The following imaging modalities are commonly utilized:

Magnetic resonance imaging (MRI) has excellent spatial resolution, soft tissue contrast, and it can detect soft tissue fluid; however, it may not be able to reliably detect the presence of air along fascial planes. Multiplanar images can be obtained without the use of ionizing radiation, which is an advantage that is not seen with computerized tomography. However, there is some concern that this modality is too sensitive, and cannot differentiate between inflammation, necrotizing fasciitis, and cellulitis.

Computerized tomography (CT) scanning compares favorably with MRI in its ability to detect soft tissue infections. Unlike MRI, it requires the use of ionizing radiation. It has been suggested that an emergent non-contrast CT scan to detect air along the fascial plane, may be the best imaging study to obtain to promptly confirm the presence of a NSTI.

For traumatic or spontaneous gas gangrene, either MRI or CT can be obtained to determine if the infection is limited to the muscle, or has extended to involve fascial planes.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Plain radiographs are often obtained to determine if soft tissue gas is present; however, they are often of no value in the diagnosis of NSTI.

III. Default Management.

As soon as there is a reasonable suspicion or a NSTI or gas gangrene, then surgical consultation must be sought, since this is a surgical emergency. If the patient has Fournier’s gangrene, then a urologist should be consulted.

If the patient is confirmed to have a NSTI or gas gangrene, then prompt surgical exploration and aggressive surgical debridement of the affected fascia are mandatory. For a NSTI, after the initial debridement procedure has been completed, the patient will require re-exploration in 24 hours, and this will need to be done daily, until it has been confirmed that all non-viable tissue has been resected. Many patients with a NSTI will require four or five debridement procedures during their first hospital admission.

The likely requirement for several surgical debridements over a period of many days also applies to patients with gas gangrene. At the time of the initial diagnosis of either a NSTI or gas gangrene, it may be necessary to promptly arrange for transfer to a facility that has expertise with the management of complex wounds. Some have advocated that patients with a NSTI should receive care in a burn center, but it is unclear as to whether or not this decreases mortality.

It is essential to immediately start broad-spectrum antibiotic therapy that provides adequate coverage for the most likely causative organisms. Antibiotic therapy may be eventually discontinued, that is, several days after the last surgical debridement has been performed. Currently, there are no established guidelines that specify the optimal length of treatment with antibiotic therapy.

Close monitoring of the patient’s hemodynamic status is required, in anticipation of the possible occurrence of significant clinical deterioration. For patients with type II NSTI who develop streptococcal toxic shock syndrome, which is associated with increased capillary permeability and hypotension, there may be a need for the very aggressive administration of IV fluids, that is 10-20 liters per day), and pressor support may also be required. It is important to be aware that the use of either epinephrine or norepinephrine in this setting may be associated with the development of symmetrical gangrene.

Although the benefit of using intravenous immune globulin (IVIG) for the treatment of NSTI is controversial, it is sometimes utilized. Following surgical and medical intervention, hyperbaric oxygen (HBO) has an adjunctive role in the management of NSTI. Since it is not widely available, and has not been well-studied, there is only limited evidence to support the use of HBO for the treatment of NSTI.

Some patients with NSTI may develop respiratory failure, and then will require mechanical ventilation. Initially admitting the patient to the intensive care unit (ICU) should be strongly considered, to allow for close monitoring of his or her hemodynamic status. Nutritional support (in the form of supplemental enteral or parenteral nutrition) is essential for patients with a NSTI, and this should be provided as soon as the patient is hemodynamically stable.

Postoperative wound management will be necessary after the patient undergoes surgical debridements. The placement of split-thickness skin grafts, full-thickness skin grafts, or temporary skin substitutes (such as cadaveric skin allografts or porcine skin xenografts) may be necessary, if the postoperative wound is not suitable for primary closure.

A. Immediate management.

1. Request urgent surgical consultation.

2. Broad-spectrum antibiotics must be started immediately in the emergency department. Once Gram’s stain, tissue and blood culture results become available, then antibiotic therapy can be appropriately narrowed down. Appropriate antibiotic coverage for adults with NSTIs is indicated below:

Mixed infections (usually seen in type I NSTI)

Anaerobic coverage must be provided, since the infection is usually polymicrobial. Empiric antibiotic therapy options are:

3. Intravenous fluids should be started promptly in the emergency department.

B. Physical Examination Tips to Guide Management.

Careful assessment of the areas that have been surgically debrided is important, to ensure that the NSTI or gas gangrene has been adequately treated. If there are any skin areas that are concerning, then the surgeon should be advised about this, since the patient may require another debridement procedure.

Obtain a CBC once daily, until the leukocytosis has resolved for patients who have a NSTI. Since intravascular hemolysis can occur in bacteremic patients with traumatic gas gangrene, they require a daily CBC, until repeat blood cultures become negative.

D. Long-term management.

Long-term management of the NTSI or gas gangrene, that is, after the patient has undergone surgical debridement procedures, would most likely be coordinated by the surgeon. This is because the patient may have extensive surgical wounds, for which a skin graft or temporary skin substitute may be needed for closure. Surgical follow-up would be necessary to ensure that these wounds are adequately addressed.

E. Common Pitfalls and Side-Effects of Management.

Urgent surgical consultation is required for patients suspected of having either a NSTI or Clostridial myonecrosis (gas gangrene). Do not delay surgical evaluation pending imaging studies.

Antibiotic therapy must be started immediately for patients with either a NSTI or Clostridial myonecrosis (gas gangrene).

IV. Management with Co-Morbidities.

A. Renal Insufficiency.

The antibiotics that are administered for the treatment of the NSTI or gas gangrene (Clostridial myonecrosis) would need to be renally dosed.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure.

Since patients with NSTI and gas gangrene often require fluid resuscitation, care would need to be taken to avoid the development of acute decompensated heart failure, as a result of the aggressive administration of IV fluids.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management.

E. Diabetes or other Endocrine issues.

Consistent glycemic control will be important to promote healing of the surgical wounds.

F. Malignancy.

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc.).

No change in standard management.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

Most patients with these severe infections will require nutritional support.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

Careful monitoring of all surgically debrided areas is important to ensure that evidence of a NSTI does not recur. This would be an indication for the patient to promptly undergo additional surgical debridement.

Monitor the hemoglobin in a bacteremic patient with traumatic gas gangrene (Clostridial myonecrosis), since intravascular hemolysis may develop (and is associated with increased morbidity and mortality).

B. Anticipated Length of Stay.

A patient who presents with a NSTI or gas gangrene (Clostridial myonecrosis) will likely require multiple surgical debridements, and often requires stabilization in the ICU during his or her hospital admission. For survivors of NSTI, the mean length of stay in the ICU is 21 days, and the mean hospital length of stay is 32 days.

C. When is the Patient Ready for Discharge?

The patient is stable for discharge when:

1. There is no evidence that a NSTI or gas gangrene (Clostridial myonecrosis) is still present, including no signs of systemic toxicity.

2. The surgically debrided wounds have a favorable appearance.

D. Arranging for Clinic Follow-up.

1. When should clinic follow up be arranged and with whom?

Surgical follow-up within 1 week, for monitoring of the wounds that resulted from surgical debridements.

If the patient can be discharged directly to home from the hospital, then arrangements should be made for a home health nurse to do regular dressing changes at the patient’s residence.

2. What tests should be conducted prior to discharge to enable best clinic first visit?

None.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit?

None.

E. Placement Considerations.

If the patient required extensive surgical debridements for treatment of the NSTI or gas gangrene (Clostridial myonecrosis), then placement in an LTAC or SNF, that is equipped to properly manage complex wounds, may be necessary.

The decision about whether or not facility placement will be necessary should be determined by consulting with the surgeon during the first few days of the patient’s admission.

F. Prognosis and Patient Counseling.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

NA

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

The importance of appropriate wound care for the wounds that developed as a result of surgical debridement, need to be stressed to the patient. Doing so may help to reduce the likelihood that an infection will develop at these sites.